Tablet Size Research Articles

BIOEQUIVALENCE STUDY OF GENERIC SALBUTAMOL TABLETS WITH LOGO AND BRANDED GENERIC

Salbutamol is a medication that stimulates beta receptors, particularly beta agonists, which are widely used as a remedy for sudden asthma attacks and those triggered by physical exercise due to its potent and rapid bronchodilating properties. These medications are known as short-acting beta-agonists (SABA). The purpose of this study was to examine in detail the significant differences in dissolution and absorption rates associated with the active ingredient in two pharmaceutically equivalent drug products, and to compare them to determine their bioequivalence. The research methodology involved experimental studies using a quantitative approach, including tests of physical quality, content determination, and dissolution testing. The results of the physical quality test for the uniformity of salbutamol tablet sizes showed that generic branded tablets, brand A, brand C, and brand D had a thickness of 0.10 cm ± 0 and a diameter of 0.50 cm ± 0, brand B had a thickness of 0.20 cm ± 0 and a diameter of 0.60 cm ± 0, and brand E had a thickness of 0.10 cm ± 0 and a diameter of 0.40 cm ± 0. The weight uniformity test results indicated that none of the generic branded tablets, brand B, or brand D deviated from columns A (7.5%) and B (15%), whereas none of the tablets from brands A, C, or E deviated from columns A (10%) and B (20%) ...

Dosage by design – 3D printing individualized cabozantinib tablets with immediate release

Production of patient-specific dosage forms is important to improve patient adherence and effectiveness while reducing the prevalence and severity of adverse effects. Due to its possibility of rapid prototyping 3D printing can be used to produce individual dosages while utilizing techniques such as hot melt extrusion to increase the bioavailability of poorly soluble drugs. In this work, Parteck MXP and Kollicoat IR were used as water-soluble polymer bases for formulation development for 3D printing of various dosages incorporating cabozantinib while enabling immediate release. The effect of tablet design and the excipients sorbitol, croscarmellose sodium, and sodium starch glycolate was investigated for this goal. A way to calculate the size of tablets for predetermined dosages is proposed to enable the printing of individual strengths from one formulation. Rheological data were collected to deepen the understanding of the role of melt viscosity in 3D printing and hot melt extrusion processes. The production of immediate-release cabozantinib tablets containing every therapeutically relevant dosage in a single unit produced by two-step 3D printing was realized.

Development of Orodispersible Tablets with Solid Dispersions of Fenofibrate and Co-Processed Mesoporous Silica for Improved Dissolution.

Poor water solubility is an important challenge in the development of oral patient-friendly solid dosage forms. This study aimed to prepare orodispersible tablets with solid dispersions of a poorly water-soluble drug fenofibrate and a co-processed excipient consisting of mesoporous silica and isomalt. This co-processed excipient, developed in a previous study, exhibited improved flow and compression properties compared to pure silica while maintaining a high specific surface area for drug adsorption. Rotary evaporation was used to formulate solid dispersions with different amounts of fenofibrate, which were evaluated for solid state properties and drug release. The solid dispersion with 30% fenofibrate showed no signs of crystallinity and had a significantly improved dissolution rate, making it the optimal sample for formulation or orodispersible tablets. The aim was to produce tablets with minimal amounts of additional excipients while achieving a drug release profile similar to the uncompressed solid dispersion. The compressed formulations met the requirements for orodispersible tablets in terms of disintegration time, and the drug release from best formulation approximated the profile of uncompressed solid dispersion. Future research should focus on reducing the disintegration time and tablet size to enhance patient acceptability further.

Factor Analysis of Patients Who Find Tablets or Capsules Difficult to Swallow Due to Their Large Size: Using the Personal Health Record Infrastructure of Electronic Medication Notebooks.

Understanding patient preference regarding taking tablet or capsule formulations plays a pivotal role in treatment efficacy and adherence. Therefore, these preferences should be taken into account when designing formulations and prescriptions. This study investigates the factors affecting patient preference in patients who have difficulties swallowing large tablets or capsules and aims to identify appropriate sizes for tablets and capsules. A robust data set was developed based on a questionnaire survey conducted from December 1, 2022, to December 7, 2022, using the harmo smartphone app operated by harmo Co, Ltd. The data set included patient input regarding their tablet and capsule preferences, personal health records (including dispensing history), and drug formulation information (available from package inserts). Based on the medication formulation information, 6 indices were set for each of the tablets or capsules that were considered difficult to swallow owing to their large size and concomitant tablets or capsules (used as controls). Receiver operating characteristic (ROC) analysis was used to evaluate the performance of each index. The index demonstrating the highest area under the curve of the ROC was selected as the best index to determine the tablet or capsule size that leads to swallowing difficulties. From the generated ROCs, the point with the highest discriminative performance that maximized the Youden index was identified, and the optimal threshold for each index was calculated. Multivariate logistic regression analysis was performed to identify the risk factors contributing to difficulty in swallowing oversized tablets or capsules. Additionally, decision tree analysis was performed to estimate the combined risk from several factors, using risk factors that were significant in the multivariate logistic regression analysis. This study analyzed 147 large tablets or capsules and 624 control tablets or capsules. The "long diameter + short diameter + thickness" index (with a 21.5 mm threshold) was identified as the best indicator for causing swallowing difficulties in patients. The multivariate logistic regression analysis (including 132 patients with swallowing difficulties and 1283 patients without) results identified the following contributory risk factors: aged <50 years (odds ratio [OR] 1.59, 95% CI 1.03-2.44), female (OR 2.54, 95% CI 1.70-3.78), dysphagia (OR 3.54, 95% CI 2.22-5.65), and taking large tablets or capsules (OR 9.74, 95% CI 5.19-18.29). The decision tree analysis results suggested an elevated risk of swallowing difficulties for patients with taking large tablets or capsules. This study identified the most appropriate index and threshold for indicating that a given tablet or capsule size will cause swallowing difficulties, as well as the contributory risk factors. Although some sampling biases (eg, only including smartphone users) may exist, our results can guide the design of patient-friendly formulations and prescriptions, promoting better medication adherence.

Pimobendan controlled release guar gum printlets: Tailoring drug doses for personalised veterinary medicines

Treating chronic heart diseases in dogs is challenging due to variations in mass within and between species. Pimobendan (PBD), a veterinary drug only, is prescribed in specific cases of chronic heart disease in dogs and is available on the market in only a few different doses. Furthermore, the therapy itself is challenging due to the large size of the chewable tablets and the requirement for twice-daily administration. The development of customised and on-demand PBD medicines by three-dimensional (3D) printing has been proposed to circumvent these disadvantages. In this study, we designed controlled-release flavoured printlets containing PBD. We evaluated the use of two natural polymers, guar or xanthan gums, as the main component of the printing inks. Guar gum showed the better rheological behavior and printability by semisolid extrusion. The printlets were produced in three different shapes and sizes to allow dose customisation. Guar gum printlets showed a PBD controlled release profile, regardless of their shape or size. Therefore, we have demonstrated a novel approach for controlling PBD drug release and tailoring the dose by employing a natural polymer to produce 3D-printed tablets. This study represents a significant step towards the development of 3D-printed guar gum controlled-release formulations for veterinary applications.

The Effect of PEG 4000 in Co-processed Excipient using Melt Granulation Method on the Physical Characteristics of Chitosan Tablets in Mangrove Crab Shells (Scylla serrata)

Mangrove Crab (Scylla serrata) is an animal that likes to be consumed but its shell waste is underutilized. The shell contains chitosan which has many benefits, one of which can lower cholesterol levels. The combination of 2 or more excipients is called co-processed excipients which are then continued into tablets by direct compression. The aim of the study was to find out whether chitosan could be formalized into coprocessed tablets (lactose, primogel, and PEG 4000 7.5% &amp; 15%) by direct compression method and the effect of differences in the characteristics of coprocessed and chitosan tablets with a ratio of PEG 4000 7.5% and 15 % as binder. The evaluation results showed that chitosan tablets fulfilled the requirements for the uniformity of weight, hardness, disintegration time (F1) tests, while they did not meet the requirements for the uniformity of tablet size, friability and disintegration times (F2) tests and the results of the coprocessing evaluation met specifications both F1 and F2, namely: particle size distribution, moisture content, flow rate, angle of repose (very good), compressibility index (adequate) and Hausner's ratio (very good). The evaluation results were then processed statistically using the SPSS application using the independent t-test method which showed that there was no significant difference in the effect of PEG 4000 7.5% and 15% as a binder on the characteristics of co-processed and chitosan tablets. Chitosan tablets from mangrove crab shells (Scylla serrata) cannot be formalized by direct compression with co-processing.

Threshold size of Tablet and Capsule : Prospective Study

Background: Medical tablets and capsules are the most commonly used dose form due to their portability. However, their enormous size frequently causes difficulties during swallowing, which might lead to decreased drug adherence. The authors examined postmarketing surveillance data to assess the size of medical tablets and capsules that patients consider too large to swallow. Aim: This study aims to learn the law behind keeping the shape or size of capsules/ tablets in higher dimensions. Method: A dataset was created from the package inserts of the reported medications based on reports from patients saying that the pill or capsule was too large for consumption. Two analyses were performed: size distribution histogram analysis and geometric analysis utilizing linear approximation. Conclusion: The size of tablets/capsules that patients consider too large to consume. As a result, while creating or modifying tablets/capsules, the drug should be scored, divided into smaller dosages, or redesigned as an orally disintegrating formulation.

Physicochemical Characterization and Reverse Engineering of Reference Market Product for Generic Formulation Development

The present study aimed to carry out reverse engineering of reference innovator product (Xarelto® 20 mg film-coated tablets) to decode the critical scientific information that is needed for successfully develop a stable and bio-equivalent generic formulation of rivaroxaban 20 mg film-coated tablets. The innovator product characterization was done followed by deformulation of the reference product (Xarelto® 20 mg film-coated tablets) to quantity critical excipients to decode the innovator product’s quantitative composition and to identify the manufacturing process used to manufacture the innovator product. The particle size distribution and particle size distribution of rivaroxaban API used in the innovator product were performed using hot-stage microscopy. The polymorphic form of rivaroxaban API used was identified using DSC and XRD methods. Visual, tactile and microscopic evaluation of granules obtained from crushed tablets of the innovator product revealed that the granulation process was used in the manufacturing of the innovator product. It was further concluded that the manufacturing process is wet granulation process due to the presence of organic solvent in the innovator core tablet. Physical evaluation was done to know the tablet weight, shape, size, coating appearance, tablet hardness and disintegration time. Chemical analysis was performed to record the drug content, percentage impurity and dissolution profile. The decoded information can serve as a reference for a faster and bioequivalent generic formulation development with reduced cost, time, effort, and a higher success rate

Drug Extended-Release System Utilizing Micelle Formation of Highly Water-Soluble Drugs and a Counter Polymer.

The objective of this study is to clarify the mechanism of extending release of highly water-soluble drugs via counter polymer (CP) utilization in poly(ethylene oxide) (PEO)/polyethylene glycol (PEG) matrix tablets. Carbomer, poly(acrylic acid), was used as a CP, which has the opposite charges to the drugs. The in vitro release of several highly water-soluble drugs from PEO/PEG tablet with or without CP were tested, the relationship between the sustained release effect by a CP (SRE) and the physicochemical properties of the drugs was investigated. The results demonstrated that the utilization of CP can extend the release of some highly water-soluble drugs by effectively controlling the drug diffusion through matrices. On the other hand, the effectiveness of CP was different depending on the drugs applied. There were not statistical correlations between SRE and physicochemical properties such as solubility, molecular weight, and charge intensity of the drugs, while a micelle forming property of the drugs played an important role in SRE by CP. It was concluded that CP, Carbomer, having negative charges could effectively interact with opposite charges on the surface of stable drug micelles, which could result in a significant decrease in drug diffusion leading to extended drug release. It is considered that the system utilizing CP is a promising approach to achieve extended release of highly water-soluble drugs with a reasonable tablet size, especially in the case of large drug loading.

Bictegravir/Emtricitabine/Tenofovir Alafenamide for HIV-1: What is the Hidden Potential of This Emerging Treatment?

Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is a single-tablet antiretroviral therapy regimen. B/F/TAF has become a popular treatment choice because of its small tablet size, high barrier to resistance, favorable tolerability, and limited drug-drug interaction profile. Continued research on B/F/TAF has revealed additional potential for this regimen. This review presents recent literature supporting the use of B/F/TAF as an option for consolidating therapy and maintaining virologic suppression in individuals despite M184V/I mutations. Additionally, children are a unique patient population with limited antiviral options. Standard dose B/F/TAF has demonstrated similar drug exposure in children and adolescents as adults, and low-dose B/F/TAF is approved for children living with HIV greater than two years of age and weighing at least 14 kg. Data supporting this recommendation is described in this review. Finally, despite a lack of prospective data, B/F/TAF may have a role in the future of pre- and post-exposure prophylaxis. This review discusses these discoveries and the continued exploration of the hidden potential of B/F/TAF.

Computer numerical control (CNC) carving as an on-demand point-of-care manufacturing of solid dosage form: A digital alternative method for 3D printing

Computer numerical control (CNC) carving is a widely used method of industrial subtractive manufacturing of wood, plastics, and metal products. However, there have been no previous reports of applying this approach to manufacture medicines. In this work, the novel method of tablet production using CNC carving is introduced for the first time. This report provides a proof-of-concept for applying subtractive manufacturing as an alternative to formative (powder compression) and additive (3D printing) manufacturing for the on-demand production of solid dosage forms. This exemplar manufacturing approach was employed to produce patient-specific hydrocortisone (HC) tablets for the treatment of children with congenital adrenal hyperplasia. A specially made drug-polymer cast based on polyethene glycol (PEG 6,000) and hydroxypropyl cellulose was produced using thermal casting. The cast was used as a workpiece and digitally carved using a small-scale 3-dimensional (3D) CNC carving. To establish the ability of this new approach to provide an accurate dose of HC, four different sizes of CNC carved tablet were manufactured to achieve HC doses of 2.5, 5, 7.5 and 10 mg with a relative standard deviation of the tablet weight in the range of 3.69–4.79%. In addition, batches of 2.5 and 5 mg HC tablets met the British Pharmacopeia standards for weight uniformity. Thermal analysis and X-ray powder diffraction indicated that the model drug was in amorphous form. In addition, HPLC analysis indicated a level of purity of 96.5 ± 1.1% of HC. In addition, the process yielded mechanically strong cylindrical tablets with tensile strength ranging from 0.49 to 1.6 MPa and friability values of <1%, whilst maintaining an aesthetic look. In vitro, HC release from the CNC-carved tablets was slower with larger tablet sizes and higher binder contents. This is the first report on applying CNC carving in the pharmaceutical context of producing solid dosage forms. The work showed the potential of this technology as an alternative method for the on-demand manufacturing of patient-specific dosage forms.

Assessment of satisfaction with antiretroviral drugs and the need for long-acting injectable medicines among people living with HIV in Japan and its associated factors: a prospective multicenter cross-sectional observational study

BackgroundLong-acting injectable formulations for HIV infection have been approved and are now available in Japan. Although not currently recommended as first-line drugs in Japanese or overseas guidelines, use of such formulations may increase, in accordance with patient conditions and preference. We determine the level of satisfaction with current anti-HIV drugs and analyzed the preferences of patients who favor long-acting injectable drugs based on their satisfaction level with the present anti-HIV drugs.MethodsPeople living with HIV (PLWH) who had received antiretroviral therapy (ART) for at least one month and consented to the study between 1 April and 31 December 2021 were included in a survey conducted using a self-administered questionnaire. The content of the survey included satisfaction with seven items (tablet size, ease and feeling when taking the medicine, color, taste, portability, daily oral therapy, and co-payment) related to the anti-HIV drugs they were taking and their need for future drugs (dosage form, frequency of dosing, long-acting injectable, etc.). In addition, factors related to the need for long-acting injectable medications were analyzed with regard to the relationship with satisfaction with anti-HIV drugs.ResultsOverall, 667 patients available for analysis were included in this study. Satisfaction with anti-HIV drugs was highest with regard to “co-payment” and lowest with “daily oral therapy”. Regarding the need for long-acting injectable medications, logistic regression analysis indicated that tablet size and daily oral therapy were significant predictors of patient preference for a once-every-eight-weeks intramuscular formulation in terms of their requirement for long-acting injectable medications (tablet size, OR = 2.14, 95%CI 1.030–4.430, p = 0.042; and daily oral therapy, OR = 1.75, 95%CI 1.010–3.030, p = 0.044).ConclusionsPatients currently receiving anti-HIV drugs who express dissatisfaction with tablet size and daily oral therapy may prefer a long-acting injectable formulation, taking into consideration patient age, employment status, ART history, frequency of daily dosage and concomitant medications other than ART.

Evaluating the Acceptability, Swallowability, and Palatability of Film-Coated Mini-Tablet Formulation in Young Children: Results from an Open-Label, Single-Dose, Cross-Over Study.

Mini-tablets are advantageous over liquid formulations in overcoming challenges related to stability, taste, and dosage. This open-label, single-dose, cross-over study investigated the acceptability and safety of drug-free, film-coated mini-tablets in children aged 1 month-6 years (stratified: 4-6 years, 2-<4 years, 1-<2 years, 6-<12 months, and 1-<6 months), and their preference for swallowing either a high quantity of 2.0 mm or a low quantity of 2.5 mm diameter mini-tablets. The primary endpoint was acceptability derived from swallowability. The secondary endpoints were investigator-observed palatability, acceptability as a composite endpoint derived from both swallowability and palatability, and safety. Of 320 children randomized, 319 completed the study. Across all tablet sizes, quantities and age groups, acceptability rates based on swallowability were high (at least 87%). Palatability was rated as "pleasant/neutral" in 96.6% of children. The acceptability rates as per the composite endpoint were at least 77% and 86% for the 2.0 mm and 2.5 mm film-coated mini-tablets, respectively. No adverse events or deaths were reported. Recruitment in the 1-<6-months group was stopped early due to coughing-evaluated as "choked on" in three children. Both 2.0 mm and 2.5 mm film-coated mini-tablets are suitable formulations for young children.

A novel abiraterone acetate oral suspension for patients with metastatic prostate cancer: An open-label, phase 3, randomized trial.

5052 Background: Abiraterone acetate (AA) is a first-line oral hormone therapy for metastatic prostate cancer (mPC), but the licensed formulation is limited by large tablet size, requirement to take on an empty stomach, and pharmacokinetic variability. TAVT-45, a novel formulation of AA granules for oral suspension, offers improved oral bioavailability (allowing dose reduction), decreased food effect, and may provide an option for the ~20-30% of patients with dysphagia. This Phase 3, open-label global study (NCT04887506) aimed to establish therapeutic equivalence between TAVT-45 granules and reference AA tablets (R-AA). Methods: Patients with castrate-resistant or castrate-sensitive mPC (mCRPC or mCSPC) were randomized 1:1 to receive TAVT-45 (1 sachet of AA granules [250 mg] in water or juice, twice daily) or R-AA tablets (2 x 500 mg once daily ≥1 h before or ≥2 h after food), plus prednisone (5 mg once [mCSPC] or twice [mCRPC] daily) for 84 days. Efficacy (serum testosterone and prostate-specific antigen [PSA]) and safety were assessed. Average serum testosterone concentrations on Days 9 &amp; 10 (primary endpoint, analyzed via analysis of covariance) were compared to show therapeutic equivalence. The key secondary endpoint was PSA-50 response (patients with ≥50% decrease in PSA from baseline at any time). mCRPC was the primary analysis population. Preliminary results are presented. Results: Of 107 randomized patients, 103 received TAVT-45 (n=54) or R-AA (n=49). The TAVT-45 and R-AA groups were well matched (mean [SD] age: 74.5 [8.45] and 74.9 [8.40] years; mCRPC: 61.1% and 61.2%). In mCRPC, serum testosterone concentrations fell rapidly from mean (SD) baseline of 9.7 (5.19) for TAVT-45 and 10.6 (7.32) ng/dL for R-AA, with all &lt;1 ng/dL by Day 9. Therapeutic equivalence between TAVT-45 and R-AA at Days 9 &amp; 10 was also shown in the full study population: Days 9 &amp; 10 average rounded-up least-squares mean serum testosterone levels were comparable (TAVT-45 [n=52]: 1.004 ng/dL; R-AA [n=47]: 1.015 ng/dL), and the geometric mean ratio between groups was 0.990 (90% CI: 0.978-1.002), with the 90% CI falling within 80.0–125.0% equivalence limits. No statistical difference between TAVT-45 vs R-AA was demonstrated for PSA-50 (mCRPC 85% vs 70%; mCSPC 90% vs 95%). The frequency of treatment-emergent adverse events (TEAEs) was similar between groups; most were mild or moderate. Serious TEAEs occurred in 5 TAVT-45 and 3 R-AA patients. There were two deaths in treated patients due to cardiorespiratory arrest (TAVT-45) and prostate cancer (R-AA); neither was considered related to study drug. Conclusions: This Phase 3 study demonstrates that TAVT-45, a novel AA formulation with improved bioavailability, yields similar testosterone/PSA responses and a comparable safety profile to R-AA, and as an oral solution, may be suitable for mPC patients with dysphagia. Clinical trial information: NCT04887506 .

Influence of Solid Oral Dosage Form Characteristics on Swallowability, Visual Perception, and Handling in Older Adults.

Swallowability, visual perception, and any handling to be conducted prior to use are all influence factors on the acceptability of an oral dosage form by the patient. Knowing the dosage form preferences of older adults, as the major group of medication end users, is needed for patient-centric drug development. This study aimed at evaluating the ability of older adults to handle tablets as well as to assess the anticipated swallowability of tablets, capsules, and mini tablets based on visual perception. The randomized intervention study included 52 older adults (65 to 94 years) and 52 younger adults (19 to 36 years). Within the tested tablets, ranging from 125 mg up to 1000 mg in weight and being of different shapes, handling was not seen as the limiting factor for the decision on appropriate tablet size. However, the smallest sized tablets were rated worst. According to visual perception, the limit of acceptable tablet size was reached at around 250 mg for older adults. For younger adults, this limit was shifted to higher weights and was dependent on the tablet shape. Differences in anticipated swallowability with respect to tablet shapes were most pronounced for tablets of 500 mg and 750 mg in weight, independent of the age category. Capsules performed worse compared to tablets, while mini tablets appeared as a possible alternative dosage form to tablets of higher weight. Within the deglutition part of this study, swallowability capabilities of the same populations were assessed and have been reported previously. Comparing the present results with the swallowing capabilities of the same populations with respect to tablets, it shows adults' clear self-underestimation of their ability to swallow tablets independent of their age.

Meeting Challenges of Pediatric Drug Delivery: The Potential of Orally Fast Disintegrating Tablets for Infants and Children.

A majority of therapeutics are not available as suitable dosage forms for administration to pediatric patients. The first part of this review provides an overview of clinical and technological challenges and opportunities in the development of child-friendly dosage forms such as taste masking, tablet size, flexibility of dose administration, excipient safety and acceptability. In this context, developmental pharmacology, rapid onset of action in pediatric emergency situations, regulatory and socioeconomic aspects are also reviewed and illustrated with clinical case studies. The second part of this work discusses the example of Orally Dispersible Tablets (ODTs) as a child-friendly drug delivery strategy. Inorganic particulate drug carriers can thereby be used as multifunctional excipients offering a potential solution to address unique medical needs in infants and children while maintaining a favorable excipient safety and acceptability profile in these vulnerable patient populations.

Impact of Tablet Size and Shape on the Swallowability in Older Adults.

Older adults represent the major target population for oral medications, due to the high prevalence of multimorbidity. To allow for successful pharmacological treatments, patients need to adhere to their medication and, thus, patient-centric drug products with a high level of acceptability by the end users are needed. However, knowledge on the appropriate size and shape of solid oral dosage forms, as the most commonly used dosage forms in older adults, is still scarce. A randomized intervention study was performed including 52 older adults (65 to 94 years) and 52 young adults (19 to 36 years). Each participant swallowed four coated placebo tablets differing in weight (250 to 1000 mg) and shape (oval, round, oblong) in a blinded manner on three study days. The choice of tablet dimensions allowed for a systematic comparison between different tablet sizes of the same shape, as well as between different tablet shapes. Swallowability was assessed using a questionnaire-based method. All tested tablets were swallowed by ≥80% of adults, independent of age. However, only the 250 mg oval tablet was classified as well swallowable by ≥80% of old participants. The same was true for young participants; however, they also considered the 250 mg round and the 500 mg oval tablet as well swallowable. Furthermore, swallowability was seen to influence the willingness to take a tablet on a daily basis, especially for an intake over longer time periods.

Investigation of Information Printed on The Blister Pack of Loxoprofen Sodium Tablets

Introduction: Loxoprofen sodium was selected as a commonly used medicine. The loxoprofen sodium tablets are marketed by 22 companies in Japan. The 22 different packaging types for this single active ingredient are served. We investigated the specifications printed on the 10-tablet blister pack. Methods: Regarding specifications printing, using the 22 loxoprofen sodium products, the survey items included how many times each of the specific printing was printed on the 10-tablet blister pack. About the questionnaire survey, a question I assessed the desired number of specifications. Question II assessed the direct printing of the drug name on each of the tablets and the size of tablet. The target population of the survey consisted of prescribing doctors, nurses, pharmacists, and non-healthcare workers. Result: The number of instances in which the drug name was listed ranged from 3 to 22 on the 10-tablet blister pack. The tablet identification code was printed ranged 0 - 10. Eleven products had no medical effect information on the pack. The expiration date was printed on two products. The serial number was not printed on one product. On the questionnaire survey, the desired number of instances that the standard dose was printed was significantly higher for nurses and pharmacists than for prescribing doctors and non-healthcare workers. Nurses considered information about medical effects to be important. Pharmacists demanded more barcodes. Several identification codes were requested by health care professionals. Although many of the tablets were 9 mm in size, the respondents desired smaller tablets. Conclusion: There were gaps between the amount of information printed on the pack and that was considered desirable by healthcare professionals and non-healthcare workers. Our findings indicate that multiple items are considered useful for developing packages for oral drugs marketed in the future as well as in ensuring safe and secure pharmacological therapy

Stability of Abuse-deterrent properties of PEO-based Abuse-deterrent formulation

Abuse of opioid drug products is a national health crisis in the US. To deter abuse, a number of drug products with abuse-deterrent (AD) properties have been approved by the US Food and Drug Administration (FDA). For abuse deterrence, it is critical to maintain the AD properties during the product shelf life. However, no information on the stability of AD properties during product shelf life is publicly available. In this study, stability of AD properties of surrogate AD formulation (ADF) of opioid active pharmaceutical ingredients (APIs) were studied. Surrogate extended release (ER) AD tablets were prepared by direct compression using Diltiazem HCl (model drug), polyethylene oxide (PEO WSR 301) polymer and magnesium stearate followed by curing at 70 °C for 30 mins. The stability studies were conducted at 25 °C/60 % RH and 40 °C/75 % RH storage conditions for 12 months (M) and 6 months (M), respectively. In vitro characterization and evaluation of AD properties of tablets were performed. As anticipated, the curing process increased the crushing strength of the tablets. However, the tablets could still be manipulated and compromised leading to an enhancement in the amount of drug extracted in solvents (e.g., water, alcohol), regardless of extraction temperature as well as tablet storage condition and time. Furthermore, the granule particle size as well as viscosity in water of manipulated samples were found to be lower for tablets stored at 25 °C/60 % RH or 40 °C/75 % RH for 12 M or 3 M/6M, respectively. The changes in AD properties eased the syringeability of hydrated samples and ultimately led to the withdrawal of higher amounts of drug into the syringe, thereby, impacting the abuse deterrence potential of the formulation by an IV route. These data demonstrated that the stability of AD properties (i.e., granule particle size, viscosity and syringeability-injectability) of PEO-based tablets was dependent on the storage condition. In conclusion, the design of AD formulation and setting of product quality profile should take into consideration the stability of AD properties during the product shelf life.

THE ANTI-INFLAMMATORY TABLET FORMULATION OF COLEUS (PLECTRANTHUS SCUTELLARIODES) LEAVES EXTRACT USING KOLLICOAT®PROTECT COATING

Objective: The purpose of this study was to find the concentration of weight gain on the use of Kollicoat®Protect to produce coleus leaf extract film-coated tablets with good physical properties.&#x0D; Methods: Coleus extract was obtained by maceration using 70% ethanol. Tablet cores were prepared using the wet granulation method, then evaluated (uniformity of weight, size, hardness, friability, and disintegration time). Coated tablets were made in four variations of polymer weight gain, i.e. 5, 6, 7, and 8%. To determine the effect of the weight gain concentration of Kollicoat®Protect an evaluation of the coated tablets was carried out, i.e. the uniformity of weight, size, hardness, disintegration time, and physical appearance of the film-coated tablets.&#x0D; Results: The four variations (Film Coated Tablet, FCT 5, 6, 7, and 8%) in weight gain of film-coated tablets showed the physical appearance results per the applicable requirements. However, the physical observation test at room temperature showed the instability of the film-coated tablet. The qualitative analysis of thin-layer chromatography showed that the productive substances in the extracts, tablet cores, and film-coated tablets were still contained even though they had undergone several formulation stages.&#x0D; Conclusion: Film-coated tablets met the standards of the Indonesian Pharmacopoeia and the United States Pharmacopeia. After two weeks, there was slight instability in film-coated tablets at room temperature storage. The extract, tablet core, and film-coated tablet contain flavonoids.